Cited by 308Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMedicinal Plants and Neuroprotection

Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice

Arendash, Gary W., Mori, Takashi, Cao, Chuanhai, Mamcarz, Malgorzata, Runfeldt, Melissa, Dickson, Alexander, Rezai-Zadeh, Kavon, Tan, Jun +4 more·2009·Journal of Alzheimer s Disease

Abstract

We have recently shown that Alzheimer's disease (AD) transgenic mice given a moderate level of caffeine intake (the human equivalent of 5 cups of coffee per day) are protected from development of otherwise certain cognitive impairment and have decreased hippocampal amyloid-beta (Abeta) levels due to suppression of both beta-secretase (BACE1) and presenilin 1 (PS1)/gamma-secretase expression. To determine if caffeine intake can have beneficial effects in "aged" APPsw mice already demonstrating cognitive impairment, we administered caffeine in the drinking water of 18-19 month old APPsw mice that were impaired in working memory. At 4-5 weeks into caffeine treatment, those impaired transgenic mice given caffeine (Tg/Caff) exhibited vastly superior working memory compared to the continuing impairment of control transgenic mice. In addition, Tg/Caff mice had substantially reduced Abeta deposition in hippocampus (decrease 40%) and entorhinal cortex (decrease 46%), as well as correlated decreases in brain soluble Abeta levels. Mechanistically, evidence is provided that caffeine suppression of BACE1 involves the cRaf-1/NFkappaB pathway. We also determined that caffeine concentrations within human physiological range effectively reduce active and total glycogen synthase kinase 3 levels in SweAPP N2a cells. Even with pre-existing and substantial Abeta burden, aged APPsw mice exhibited memory restoration and reversal of AD pathology, suggesting a treatment potential of caffeine in cases of established AD.

Integrity signals

Registry

Crossref · 10.3233/jad-2009-1087

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • For some psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms and slow the progression of neurodegeneration, although these findings are equivocal with some studies reporting caffeine increases depressive symptoms.

    “For some psychiatric illness, such as Parkinson’s disease, Alzheimer’s disease, and depression, caffeine antagonism of adenosine receptors may improve symptoms (204, 205) and slow the progression of neurodegeneration (206, 207), although these findings are equivocal with some studies reporting caffeine increases depressive symptoms (208).”

    From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [204]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Arendash, G. W., Mori, T., Cao, C., Mamcarz, M., Runfeldt, M., Dickson, A., Rezai-Zadeh, K., Tan, J., Citron, B. A., Lin, X., Echeverria, V., & Potter, H.
Affiliations
  • University of South Florida (US)
  • Social Insurance Saitama Chuo Hospital (JP)
  • Department of Molecular Medicine, University of South Florida, Tampa, FL, USA
Venue
Journal of Alzheimer s Disease
Published
2009-07-01
Volume
17
Issue
3
Pages
661-680
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
OpenAlex
W2128860352
Cited by
308
References
65
Citations by year
2026: 8 · 2025: 13 · 2024: 23 · 2023: 20 · 2022: 21 · 2021: 22 · 2020: 12 · 2019: 12 · 2018: 26 · 2017: 15 · 2016: 16 · 2015: 19 · 2014: 25 · 2013: 10 · 2012: 23
FWCI
14.58
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
Funders
National Institute on Aging (P50AG025711)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords
caffeine, Alzheimer's disease
MeSH terms
Age Factors, Alzheimer Disease, Central Nervous System Stimulants, Animals, Brain, Caffeine, Cell Line, Transformed, Cognition Disorders, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Transgenic, Models, Biological, Neurons, Psychomotor Performance, Gene Expression Regulation, Enzymologic, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Cyclic AMP-Dependent Protein Kinases, Maze Learning, Proto-Oncogene Proteins c-raf, Glycogen Synthase Kinase 3, Mice, Presenilin-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review